The induction in mice of the enzyme system aryl hydrocarbon hydroxylase (AHH) by 3-methylcholanthrene (MCA) is governed by the Ah gene; mice with the dominant Ahb allele are inducible for AHH and mice with the recessive Ahd allele are noninducible. Mice of strains with each of these alleles were painted with MCA: in the AHH inducible mice MCA induces skin tumors but cannot elicit a leukemogenic response; in the noninducible mice MCA painting rarely induces skin tumors but these are so far the only mice in which it induces lymphomas. However, some of these noninducible strains appear to be resistant to these leukemogenic effects of MCA painting. From these results it appears that host factors other than noninducibility play a perhaps decisive role in the induction of lymphoma by MCA painting in noninducible mice. The objective of this proposal is to identify the nature of these host factors and to further verify preliminary results which suggest that these factors might also influence the leukemogenic response to X-irradiaton in both noninducible and inducible mice, but play no role in the occurrence of spontaneous lymphoma in either group of mice. To this end mice of inbred strains either inducible for AHH or noninducible as well as hybrids of the cross between these strains will be observed for the development of lymphoma untreated, after receiving MCA paintings or after X-irradiation.